The overall goal of this proposal is to understand the virologic, immunologic, and clinical consequences of treating individuals during acute and early HIV-1 infection with a combination of highly active antiretroviral therapy (HMRT) and immune-based therapies. We will assess the degree of viral suppression of HMRT regimens with novel virologic assays developed at the Aaron Diamond AIDS Research Center (ADARC). We will explore the use of newly developed HIV-1 vaccines in single-site and collaborative trials to stimulate HIV-1 specific immune responses after prolonged treatment with HMRT, which had been initiated within 90 days or so of acquiring HIV-1 infection. We will also participate in single-site and collaborative randomized trials to assess the benefits of early and limited intervention with HMRT alone versus HMRT combined with immune based therapies. We hypothesize that these therapeutic manipulations may alter the post-treatment discontinuation virologic setpoint favorably, significantly anddelaying the need for initiating chronic antiretroviral therapy. With the intensive study of virologic and immunologic events during early infection, treatment, and post-treatment discontinuation, in well genetically characterized hosts, we aim to increase the understanding of how virologic, immunologic, and genetic factors converge to determine the virologic setpoint in an HIV-1 infected individual. To achieve these goals we have assembled a consortium of 3 New York City HIV/AIDS programs; the main site at ADARCI Rockefeller University, a current AIEDRP site and 2 sub sites at SUNY Downstate and Columbia University. All 3 HIV/AIDS programs are distinguished by their commitment to performing high quality clinical research. Both SUNY Downstate and Columbia are situated in highly HIV-1 affected locales with a diverse patient population from which to recruit study subjects and to perform well-needed community outreach. Investigators at ADARC, well known for commitment to translational research in HIV-1 will provide the scientific leadership and support for the site. As part of the AIEDRP the ADARC-Downstate-Columbia combined site will perform high quality basic and clinical research, single site and collaborative projects with other AIEDRP sites, and the study of acute and early HIV-1 infection in a diverse population of individuals.